Pituitary-hormone secretion by thyrotropinomas

Hormone secretion by somatotropinomas, corticotropinomas and prolactinomas exhibits increased pulse frequency, basal and pulsatile secretion, accompanied by greater disorderliness. Increased concentrations of growth hormone (GH) or prolactin (PRL) are observed in about 30% of thyrotropinomas leading to acromegaly or disturbed sexual functions beyond thyrotropin (TSH)-induced hyperthyroidism. Regulation of non-TSH pituitary hormones in this context is not well understood. We there therefore evaluated TSH, GH and PRL secretion in 6 patients with up-to-date analytical and mathematical tools by 24-h blood sampling at 10-min intervals in a clinical research laboratory. The profiles were analyzed with a new deconvolution method, approximate entropy, cross-approximate entropy, cross-correlation and cosinor regression. TSH burst frequency and basal and pulsatile secretion were increased in patients compared with controls. TSH secretion patterns in patients were more irregular, but the diurnal rhythm was preserved at a higher mean with a 2.5 h phase delay. Although only one patient had clinical acromegaly, GH secretion and IGF-I levels were increased in two other patients and all three had a significant cross-correlation between the GH and TSH. PRL secretion was increased in one patient, but all patients had a significant cross-correlation with TSH and showed decreased PRL regularity. Cross-ApEn synchrony between TSH and GH did not differ between patients and controls, but TSH and PRL synchrony was reduced in patients. We conclude that TSH secretion by thyrotropinomas shares many characteristics of other pituitary hormone-secreting adenomas. In addition, abnormalities in GH and PRL secretion exist ranging from decreased (joint) regularity to overt hypersecretion, although not always clinically obvious, suggesting tumoral transformation of thyrotrope lineage cells

Diminished and irregular thyrotropin secretion with preserved diurnal rhythm in patients with active acromegaly

The hypothalamo-pituitary-thyroid axis in acromegaly may be altered. Previous studies report diminished serum TSH concentrations in patients with active acromegaly and decreased response to TRH. On the other hand, most patients have normal thyroid hormone concentrations. Our aim was to analyze serum TSH profiles in relation to GH profiles in patients with untreated acromegaly, in order to delineate aberrations in the hypothalamo-pituitary-thyroid system. Twenty-one patients with active acromegaly and matched controls underwent a 24-h, 10-min blood sampling study. GH and TSH data were analyzed with a newly developed automated deconvolution program, approximate entropy, and cosinor regression. Basal (10.4 +/- 2.0 vs. 13.8 +/- 1.4 mU/liter . 24 h; P = 0.02) and pulsatile (11.4 +/- 1.7 vs. 18.6 +/- 1.6 mU/liter . 24 h; P = 0.002) TSH secretion was decreased in patients. TSH secretory regularity was diminished with loss of pattern synchrony between TSH and GH. Total TSH secretion correlated with TSH increase after TRH (R = 0.75; P = 0.0001), negatively with the log-transformed GH secretion rate (R = -0.52; P = 0.001), but not with adenoma size. The diurnal TSH rhythm was preserved. Total and free T4 concentrations were similar in patients and controls. Basal and pulsatile TSH secretion is decreased in active acromegaly, although T4 levels are unaffected. Diminished TSH secretion is compatible with enhanced restraint by tumoral GH feedback-driven somatostatin outflow, explaining also the reduced regularity of TSH secretion. Unchanged T4 concentrations might reflect decreased sympathetic function in GH excess states, heightening responsiveness of the thyroid gland to TS

Diminished and irregular TSH secretion with delayed acrophase in patients with Cushing's syndrome

The hypothalamus-pituitary-thyroid axis in Cushing's syndrome may be altered. Previous reports have shown diminished serum TSH concentration and decreased response to TRH. We analyzed serum TSH profiles in relation to cortisol profiles in patients with hypercortisolism of pituitary (n=16) or primary-adrenal origin (n=11) and after remission by pituitary surgery (n=7) in order to delineate aberrations in the hypothalamus-pituitary-thyroid system. Patients and controls (n=27) underwent a 24-h blood sampling study. Serum TSH and cortisol were measured with precise methods, and data were analyzed with a deconvolution program, approximate entropy (ApEn), and cosinor regression. Pulsatile TSH secretion and mean TSH pulse mass were diminished during hypercortisolism, independently of etiology (P <0.001). TSH secretion was increased in patients in remission only during daytime due to increased basal secretion (P <0.01). Pulse frequency and half life of TSH were similar in patients and controls. TSH ApEn (irregularity) was increased in patients with hypercortisolism (P <0.01), but was normal in cured patients. Cross-ApEn between TSH and cortisol, a measure of pattern synchrony loss, was increased in active disease, indicating (partial) loss of secretory synchrony. The TSH rhythm was phase delayed in hypercortisolemic patients, but normal in cured patients (P <0.01). Free thyroxine levels were decreased only in pituitary-dependent hypercortisolism compared with controls (P=0.003). Total 24-h TSH correlated negatively and linearly with log-transformed cortisol secretion (R=0.43, P=0.001). Cortisol excess decreases TSH secretion by diminishing pulsatile release, whereas surgically cured patients have elevated nonpulsatile TSH release. Diminished TSH secretory regularity in active disease suggests glucocorticoid-induced dysregulation of TRH or somatostatinergic/annexin-1 contro

Association between sex hormone-binding globulin levels and activated protein C resistance in explaining the risk of thrombosis in users of oral contraceptives containing different progestogens \ud

BACKGROUND: Epidemiological studies have shown that both the estrogen dose and progestogen type of oral contraceptives contribute to the increased risk of thrombosis in oral contraceptive users. Thrombin generation-based activated protein C (APC) sensitivity is a global test for the net prothrombotic effect of oral contraceptives and predicts the thrombotic risk. Our objective was to test the usefulness of sex hormone-binding globulin (SHBG) as a marker for the thrombotic risk of an oral contraceptive. METHODS: We measured SHBG and APC resistance in 156 healthy users of various types of oral contraceptives. RESULTS: Users of oral contraceptives with a moderately increased risk of thrombosis (gestodene and desogestrel pills) had higher SHBG levels than users of low-risk oral contraceptives containing levonorgestrel. Similarly, for higher doses of estrogen in oral contraceptives we found higher SHBG levels. Women using oral contraceptives with the highest thrombotic risk (cyproterone acetate pills) rendered the highest SHBG levels. Users of oral contraceptives containing gestodene, desogestrel or cyproterone acetate were more resistant to APC than users of levonorgestrel pills. SHBG levels were positively associated with the increased APC resistance. CONCLUSIONS: Our findings support the hypothesis that the effect of an oral contraceptive on SHBG levels might be a marker for the thrombotic risk. \u